Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA253587 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:TMPRSS2 is an androgen-regulated cell surface serine protease expressed predominantly in prostate epithelium. TMPRSS2 is expressed highly in localized high-grade prostate cancers and in the majority of human prostate cancer metastasis. Through the generation of mouse models with a targeted deletion of Tmprss2, we demonstrate that the activity of this protease regulates cancer cell invasion and metastasis to distant organs. By screening combinatorial peptide libraries we identified a spectrum of TMPRSS2 substrates that include pro-hepatocyte growth factor (HGF). HGF activated by TMPRSS2 promoted c-Met receptor tyrosine kinase signaling, and initiated a pro-invasive EMT phenotype. Chemical library screens identified a potent bioavailable TMPRSS2 inhibitor that suppressed prostate cancer metastasis in vivo. Together, these findings provide a mechanistic link between androgen-regulated signaling programs and prostate cancer metastasis that operate via context-dependent interactions with extracellular constituents of the tumor microenvironment. Custom mouse cDNA microarrays were used to measure transcript levels in microdissected anterior prostate tumors from Tmprss2+/+;TRAMP mice, Tmprss2-/-;TRAMP mice or strain-matched benign epithelium. All samples were laser-capture microdissected and total RNA isolated and amplified prior to hybridization against a reference pool of normal adult mouse tissues.
2014-09-09 | E-GEOD-58822 | biostudies-arrayexpress
Project description:TMPRSS2 is an androgen-regulated cell surface serine protease expressed predominantly in prostate epithelium. TMPRSS2 is expressed highly in localized high-grade prostate cancers and in the majority of human prostate cancer metastasis. Through the generation of mouse models with a targeted deletion of Tmprss2, we demonstrate that the activity of this protease regulates cancer cell invasion and metastasis to distant organs. By screening combinatorial peptide libraries we identified a spectrum of TMPRSS2 substrates that include pro-hepatocyte growth factor (HGF). HGF activated by TMPRSS2 promoted c-Met receptor tyrosine kinase signaling, and initiated a pro-invasive EMT phenotype. Chemical library screens identified a potent bioavailable TMPRSS2 inhibitor that suppressed prostate cancer metastasis in vivo. Together, these findings provide a mechanistic link between androgen-regulated signaling programs and prostate cancer metastasis that operate via context-dependent interactions with extracellular constituents of the tumor microenvironment.
2014-09-09 | GSE58822 | GEO
Project description:This SuperSeries is composed of the following subset Series: GSE28948: TMPRSS2-ERG, HDACs and EZH2 are involved in an AR-centric transcriptional circuitry that calibrates androgenic response for prostate cancer progression (gene expression data) GSE28950: TMPRSS2-ERG, HDACs and EZH2 are involved in an AR-centric transcriptional circuitry that calibrates androgenic response for prostate cancer progression (ChIP-Seq data) GSE35540: TMPRSS2-ERG, HDACs and EZH2 are involved in an AR centric transcriptional circuitry that calibrates androgenic response for prostate cancer progression (gene expression after ERG KD) Refer to individual Series
2012-04-26 | E-GEOD-28951 | biostudies-arrayexpress
Project description:Introgressed variants from other species can be an important source of genetic variation because they may arise rapidly, can include multiple mutations on a single haplotype, and have often been pretested by selection in the species of origin. Although introgressed alleles are generally deleterious, several studies have reported introgression as the source of adaptive alleles-including the rodenticide-resistant variant of Vkorc1 that introgressed from Mus spretus into European populations of Mus musculus domesticus. Here, we conducted bidirectional genome scans to characterize introgressed regions into one wild population of M. spretus from Spain and three wild populations of M. m. domesticus from France, Germany, and Iran. Despite the fact that these species show considerable intrinsic postzygotic reproductive isolation, introgression was observed in all individuals, including in the M. musculus reference genome (GRCm38). Mus spretus individuals had a greater proportion of introgression compared with M. m. domesticus, and within M. m. domesticus, the proportion of introgression decreased with geographic distance from the area of sympatry. Introgression was observed on all autosomes for both species, but not on the X-chromosome in M. m. domesticus, consistent with known X-linked hybrid sterility and inviability genes that have been mapped to the M. spretus X-chromosome. Tract lengths were generally short with a few outliers of up to 2.7 Mb. Interestingly, the longest introgressed tracts were in olfactory receptor regions, and introgressed tracts were significantly enriched for olfactory receptor genes in both species, suggesting that introgression may be a source of functional novelty even between species with high barriers to gene flow.
| S-EPMC8784167 | biostudies-literature
Project description:Common epithelial cancers are believed to become more aggressive through the accumulation of multiple independent molecular events that lead to the deregulation of cell signaling. However, the discovery that the majority of prostate cancers harbor gene fusions of the 5'-untranslated region of androgen regulated TMPRSS2 promoter with ETS transcription factor family members has brought this paradigm into question1,2. TMPRSS2-ERG gene fusion is the most common molecular sub-type of prostate cancer. Recent work suggests that the TMPRSS2-ERG fusion is associated with a more aggressive clinical phenotype3. In the most advanced castration resistant prostate cancers where the androgen receptor has been inactivated, the TMPRSS2-ERG fusion remains functionally active. Here we show compelling clinical and gene expression data supporting the existence of a TMPRSS2-ERG fusion prostate cancer subclass. Using expression array profiling on 455 primary prostate tumors, we identified an 87 gene expression signature, distinguishing TMPRSS2-ERG fusion prostate cancer as a discrete molecular entity. Computational analysis suggested that this fusion signature was associated with estrogen receptor signaling. Functional studies demonstrated regulation of the TMPRSS2-ERG fusion transcript by estrogenic compounds. These data identify a previously unrecognized mechanism for regulation of the TMPRSS2-ERG, even in the absence of a functional androgen receptor, and thus may have broader implications in the treatment of prostate cancer. Keywords: Prostate cancer, Expression array, Illumina, gene fusion, TMPRSS2, ERG, Signatures, Estrogen Test Cohort: 388 cases from the population based Swedish-Watchful Waiting cohort. The cohort consists of men with localized prostate cancer (clinical stage T1-T2, Mx, N0); Validation cohort: The PhysiciansM-bM-^@M-^Y Health Study (PHS) cohort included 116 US men diagnosed with incidental prostate cancer between 1983 and 2003; 455 cases were annotated for TMPRSS2-ERG fusion. Test Set: GSM208029 ... GSM208392 Validation Set: GSM208404 ... GSM208512
2008-05-27 | E-GEOD-8402 | biostudies-arrayexpress
Project description:Translational research is commonly performed in the C57B6/J mouse strain, chosen for its genetic homogeneity and phenotypic uniformity. Here, we evaluate the suitability of the white-footed deer mouse (Peromyscus leucopus) as a model organism for aging research, offering a comparative analysis against C57B6/J and diversity outbred (DO) Mus musculus strains. Our study includes comparisons of body composition, skeletal muscle function, and cardiovascular parameters, shedding light on potential applications and limitations of P. leucopus in aging studies. Notably, P. leucopus exhibits distinct body composition characteristics, emphasizing reduced muscle force exertion and a unique metabolism, particularly in fat mass. Cardiovascular assessments showed changes in arterial stiffness, challenging conventional assumptions and highlighting the need for a nuanced interpretation of aging-related phenotypes. Our study also highlights inherent challenges associated with maintaining and phenotyping P. leucopus cohorts. Behavioral considerations, including anxiety-induced responses during handling and phenotyping assessment, pose obstacles in acquiring meaningful data. Moreover, the unique anatomy of P. leucopus necessitates careful adaptation of protocols designed for Mus musculus. While showcasing potential benefits, further extensive analyses across broader age ranges and larger cohorts are necessary to establish the reliability of P. leucopus as a robust and translatable model for aging studies.
| S-EPMC11335981 | biostudies-literature
Project description:Common epithelial cancers are believed to become more aggressive through the accumulation of multiple independent molecular events that lead to the deregulation of cell signaling. However, the discovery that the majority of prostate cancers harbor gene fusions of the 5'-untranslated region of androgen regulated TMPRSS2 promoter with ETS transcription factor family members has brought this paradigm into question1,2. TMPRSS2-ERG gene fusion is the most common molecular sub-type of prostate cancer. Recent work suggests that the TMPRSS2-ERG fusion is associated with a more aggressive clinical phenotype3. In the most advanced castration resistant prostate cancers where the androgen receptor has been inactivated, the TMPRSS2-ERG fusion remains functionally active. Here we show compelling clinical and gene expression data supporting the existence of a TMPRSS2-ERG fusion prostate cancer subclass. Using expression array profiling on 455 primary prostate tumors, we identified an 87 gene expression signature, distinguishing TMPRSS2-ERG fusion prostate cancer as a discrete molecular entity. Computational analysis suggested that this fusion signature was associated with estrogen receptor signaling. Functional studies demonstrated regulation of the TMPRSS2-ERG fusion transcript by estrogenic compounds. These data identify a previously unrecognized mechanism for regulation of the TMPRSS2-ERG, even in the absence of a functional androgen receptor, and thus may have broader implications in the treatment of prostate cancer. Keywords: Prostate cancer, Expression array, Illumina, gene fusion, TMPRSS2, ERG, Signatures, Estrogen
2008-05-28 | GSE8402 | GEO
Project description:Alternative intronic polyadenylation influences cancer metastasis and response to therapy [3'-seq]
| PRJNA369527 | ENA
Project description:Alternative intronic polyadenylation influences cancer metastasis and response to therapy [CLIP-seq]
| PRJNA369516 | ENA
Project description:Mutant Kras-induced upregulation of CD24 enhances prostate cancer stemness and bone metastasis in prostate cancer.
| PRJNA393435 | ENA